tbuckley/cabot-search huggingface dataset:
Quality improvement interventions targeting vaccine uptake in cancer patients: A systematic review.
Authors: Basil Kazi, Zain Talukdar
Journal: Journal of Clinical Oncology (2023)

e18734 Background: Patients with cancer are more susceptible to morbidity and mortality from preventable infection. Despite this, patients with cancer have low rates of vaccination and quality improvement interventions to improve their rates of vaccination have not been well studied. Methods: We searched PubMed and Cochrane Library for studies that evaluated quality improvement interventions that aimed to improve vaccine uptake in patients with cancer. We searched PubMed and Cochrane library using keywords that covered cancer, vaccines and quality improvement. Title and abstract screening, data extraction and categorization was conducted by two authors with any disagreements were resolved by consensus. Results: In total, 13 studies were identified as meeting our inclusion criteria. Studies were published from 2014 to 2022. Seven studies studied the influenza vaccine, five studied the pneumococcal vaccine, and one studied both. Twelve studies employed multiple interventions, and one study employed a single intervention. Most studies evaluated interventions designed to increase patients’ and families’ knowledge of the vaccines and interventions designed to identify vaccine-eligible patients before their visit. All studies showed improvement in vaccine uptake after implementation of the study’s interventions. Conclusions: We found a broad range of quality improvement interventions that improved pneumococcal and influenza vaccine uptake for patients with cancer. Future studies should test barriers to implementation of these interventions and review if these same interventions improve uptake of other vaccines.
Concurrent hospice healthcare utilization in the hematology/oncology patient population at veterans affairs.
Authors: Anshu Hemrajani, Shelly S. Lo, Alexi Vahlkamp, Abigail Silva, Seema Limaye
Journal: Journal of Clinical Oncology (2023)

12125 Background: The benefits of early hospice enrollment include improved quality of life and overall survival (Kumar, 2017). Yet, most oncology patients continue to receive aggressive treatments including chemotherapy, radiation therapy, and hospitalizations until close to death (Ersek, 2017). Veterans have the unique opportunity to receive concurrent hospice which allows patients enrolled in hospice to receive disease modifying treatments and other interventions not typically provided under the traditional Medicare hospice benefit. Methods: A single institution retrospective review of 72 hematology and oncology patients who enrolled in the concurrent care program at the Hines VA between 12/28/2018-4/3/2021 was conducted. Patients were eligible for the concurrent care program if they (1) had a life-limiting illness with a prognosis of less than six months (2) were willing to enroll in hospice (3) had an oncologist willing to administer cancer-directed therapy. Data were summarized with descriptive statistics including medians and percentages. Results: Patients in the concurrent care hospice program were predominantly White (69.4%) and older than 70 years of age (63.9%). Most patients were diagnosed with primary gastrointestinal (29.2%), thoracic (22.2%), or genitourinary (19.4%) malignancies. While enrolled in concurrent care hospice, 15.3% of patients visited the emergency department and 45.8% had at least one hospitalization. Few patients received cytotoxic chemotherapy (27.8%), immunotherapy (20.8%), palliative radiation (20.8%), or pain procedures (4.2%) while enrolled in concurrent care hospice. Of the 19 patients who received chemotherapy, only one patient received treatment within 7 days prior to death. The minority of patients (11.1%) received a blood product and of those patients that did, 8.3% required one to three transfusions and 2.8% required three or more transfusions. Most (91.7%) patients died while in concurrent care hospice; 21.2% died within 30 days of enrollment and 56.1% died within 31 to 180 days of enrollment. Patients were more likely to die at home (63.6%) or in inpatient hospice (13.6%) as opposed to the hospital (3%). Conclusions: Enrollment in concurrent hospice care prevents patients from having to choose between comfort care and cancer-directed treatments, which is often a barrier to early hospice enrollment (Salz, 2009). At Hines VA, most patients receiving concurrent hospice care rarely or never utilized cancer directed treatments, pain procedures, blood products, or emergency room visits/hospitalizations despite having access to these resources. Furthermore, the majority of patients died with hospice-style care at home or in inpatient hospice rather than in the hospital. This observational study demonstrates that when offered the choice to pursue cancer-directed treatments, most patients opt instead to focus on comfort care at end of life.
Care cascade of anal dysplasia screening among MSM living with HIV from a single-center outpatient clinic.
Authors: Ram Prakash Thirugnanasambandam
Journal: Journal of Clinical Oncology (2023)

e18607 Background: Anal cancer is the fourth most common cancer among people living with HIV with an incidence estimated to be 89 per 100,000 among men living with HIV who have sex with men (MSM). In comparison, the incidence of anal cancer in the general population is 1.6 per 100,000. The ANCHOR study which was a randomized control trial found that treating anal high-grade squamous intraepithelial lesions (HSIL) reduces the incidence of anal cancer by more than half. These findings provide a rationale for screening for anal dysplasia in people with HIV and could have an impact on recommendations for screening and treatment. The study also highlights the need for effective strategies to improve the screening and treatment of anal HSIL and providers trained in high-resolution anoscopy (HRA). Our goal was to determine the rate of screening for anal dysplasia among men who have sex with men (MSM) living with HIV attending our clinic and subsequent referral for HRA and completion of HRA in case of abnormal results. Methods: We assessed the rate of screening for anal dysplasia among the patients identifying as MSM (n = 305) at a large HIV clinic in Brooklyn, New York. An anal dysplasia care cascade was completed. The number of patients screened for anal dysplasia and the results of the screening were obtained from the EMR. All patients with results of Atypical Squamous cell of undetermined significance (ASCUS), Low-grade intra-epithelial neoplasia (LSIL), or High-grade intra-epithelial neoplasia (HSIL) on anal cytology were evaluated for evidence of referral for HRA and the number who completed the HRA was included in the descriptive analysis. Results: 60% of the total eligible patients included in the study were screened by anal cytology, 72% of those with abnormal cytology were referred for HRA and 37% completed the anoscopy (table 1). The patients in the age group 20-40 years were more likely to be screened. The number of patients with HSIL was low. Conclusions: The engagement of MSM clients in anal dysplasia screening and management was low based on our care cascade. Considering the results of our study, we aim to identify the barriers to screening as well as to referral and completion of HRA among MSM living with HIV in our patient population. [Table: see text]
Reevaluating the role of adjuvant chemotherapy in early-stage, resectable NSCLC with high-risk clinical and pathologic features.
Authors: Brendan Heiden, Daniel B. Eaton, Su-Hsin Chang, Yan Yan, Martin W. Schoen, Theodore Seth Thomas, Bryan F. Meyers, Benjamin D. Kozower, Varun Puri
Journal: Journal of Clinical Oncology (2023)

8572 Background: The preferred treatment for early-stage non-small cell lung cancer remains surgical resection with the consideration of adjuvant chemotherapy for tumors with certain high-risk features. It is commonly cited that such treatments confer a meager 5% 5-year survival benefit compared to observation alone. We sought to reassess the benefit of adjuvant chemotherapy using modern, real-world datasets. Methods: We performed a retrospective cohort study using a dataset from the National Cancer Database. All patients with early-stage stage NSCLC (3-5cm, node-negative) who would be eligible for adjuvant chemotherapy based on National Comprehensive Cancer Network guidelines were included (i.e., presence of at least 1 high-risk feature). High-risk clinical and pathologic features were defined as poor differentiation, tumor size (≥4cm), non-anatomic wedge resection, inadequate lymph node evaluation, vascular invasion, and visceral pleural involvement. We employed average treatment effect on the treated (ATT) weighting to match patients with similar demographic, tumor, and treatment-related variables to compare outcomes between chemotherapy versus observation groups. The primary outcome was overall survival. These findings were further validated in an independent cohort from the US Veteran Health Administration (VHA). Results: The study included 10,812 patients with early-stage NSCLC who had at least 1 high-risk feature. The frequencies of high-risk features were as follows: tumor size ≥4cm (n = 3,271, 30.3%), poor differentiation (n = 9,454, 87.4%), visceral-pleural invasion (n = 2,542, 23.5%), vascular invasion (n = 1,742, 16.11%), non-anatomic wedge resection (n = 781, 7.2%), and inadequate nodal sampling (n = 6,306, 58.3%). Despite the presence of high-risk features, only 1,427 (13.2%) patients received adjuvant chemotherapy. In the ATT weighted analysis, 1,261 (49.7%) patients received adjuvant chemotherapy and 1,278 (50.3%) patients received observation. The 5-year overall survival was 70.0% (95% CI 67.1-72.7) in the chemotherapy group versus 62.0% (95% CI 60.2-63.7%) in the observation group (absolute 5-year survival difference 8.0%). In the VHA cohort, 11.3% of patients received adjuvant chemotherapy. Similarly, the 5-year overall survival was 64.0% (95% CI 51.4-74.2) in the chemotherapy group versus 56.2% (95% CI 48.3-63.4) in the observation group (absolute 5-year survival difference 7.8%). Conclusions: These data suggest a notably larger benefit of adjuvant chemotherapy in eligible patients with high-risk clinical pathologic features compared to commonly cited statistics. With the addition of more robust treatment options in early-stage disease, adherence to adjuvant and neoadjuvant treatment guidelines may disproportionately improve early-stage NSCLC outcomes following curative-intent resection.
Trends in diagnosis of de novo metastatic hormone sensitive prostate cancer in US Veterans, 2002-2021.
Authors: Nada Al masalmeh, Ruth Douglas Etzioni, Saira Khan, Arslan Babar, Kristen Marie Sanfilippo, Robert Bruce Montgomery, Eric Marshall Knoche, Lukas Owens, Yu-Ning Wong, Martin W. Schoen
Journal: Journal of Clinical Oncology (2023)

10527 Background: The incidence of non-localized prostate cancer in the US has been increasing since 2011. While the etiology of this increase is unknown, improved detection of metastatic disease and changes in prostate-specific antigen (PSA) screening may be contributing factors. In this retrospective study, we report the frequency and characteristics of veterans with de novo metastatic prostate cancer to understand changes in the diagnosis over time. Methods: The study population consisted of veterans diagnosed with de novo metastatic Hormone Sensitive Prostate Cancer (mHSPC) with a biopsy between 2002 and 2021 in the Veterans Health Affairs Prostate Cancer Data Core were included. All patients had no prior diagnosis of prostate cancer and were classified as SEER stage ‘distant’. We collected the highest PSA within 3 months of diagnosis, age, race, and calculated the Charlson Comorbidity Index. Year of diagnosis was categorized into 5-year periods and differences over tine were assessed by chi-square linear by linear ANOVA test for linearity as appropriate. Results: 15,485 patients were diagnosed with de novo mHSPC between 2002 and 2021. The mean age was 72.9 years and the median PSA was 88.0 ng/mL. There was a 39% increase of the number of patients diagnosed with mHSPC (from 3,274 between 2002-2006 to 4,560 between 2017-2021). Mean age increased from 71.6 years between 2002-2006 to 74.4 between 2017-2021 (p &lt; 0.001). Median PSA decreased from 96.6 ng/mL in 2002-2006 to 80.3 ng/mL in 2006-2021 (p &lt; 0.001). The percentage of patients who were identified as black decreased from 29.8% between 2002-2006 to 25.4% between 2017 and 2021 (p &lt; 0.001). Mean comorbidity index increased from 3.2 between 2002-2006 to 4.5 between 2017-2021 (p &lt; 0.001). BMI increased from 26.2 between 2002-2006 to 27.2 between 2017-2021 (p &lt; 0.001). Median overall survival improved from 26.7 months in 2002-2006 to 31.7 months in 2016-2021 (p &lt; 0.001). Conclusions: Over a 20-year period, the Veterans diagnosed with prostate cancer were older, with higher comorbidities and with decreased PSA at diagnosis. Additionally, overall survival improved from 26.7 to 31.7 months. The findings of this study are consistent with a reduction in screening and more sensitive imaging modalities to detect metastatic disease combined with changes in the veteran population and improvements in treatment of mHSPC. Further study is warranted to understand these trends over the same time period. [Table: see text]
The safety, tolerability and efficacy of LP-10 in subjects with refractory moderate to severe hemorrhagic cystitis: Phase 2a multicenter dose escalation clinical trial.
Authors: Michael Chancellor, Benjamin Breyer, Shreyas S. Joshi, Christopher Smith, Melissa Kaufman, Janet Okonski, Jason Hafron
Journal: Journal of Clinical Oncology (2023)

e24064 Background: Hemorrhagic Cystitis (HC), a rare but highly morbid disease for which there are currently no FDA approved treatments, can occur in cancer survivors including patients with prostate cancer, cervical/uterine cancer and colon cancer. Lipella Pharmaceuticals received orphan disease designation for HC, and recently completed a phase 2a clinical trial of LP-10 (intravesical tacrolimus) for the treatment of HC. Methods: The LP-10 Phase 2a clinical trial was a multi-center, dose-escalation study (clinicaltrials.gov: NCT01393223). The study recruited subjects with moderate to severe refractory HC. These subjects were treated with up to two courses of LP-10 intravesical bladder instillations (liposomal formulation of tacrolimus at 2 mg, 4 mg and 8 mg). Results: Fifteen subjects were screened (14 male and 1 female) and 13 enrolled. All enrolled subjects were male with mean age 67 (range 25-89 years old) with a history of prostate cancer (n = 9), bladder cancer (n = 2) and lymphoma (n = 2). Mean duration of HC was 4 years and ranged from 1-14 years. No subject discontinued treatment or were lost to follow-up. All subjects tolerated LP-10 instillations and completed the study without report of product related serious adverse events. 12 AEs were reported in 6 subjects. Pharmacokinetic analysis demonstrated short duration of low systemic uptake of tacrolimus. A dose response was noted with higher efficacy at both the 4mg and 8 mg dose groups. After LP-10 treatment, the number of cystoscopic bleeding sites and bladder ulcerations decreased and patients’ urinary symptoms improved. Conclusions: This first phase 2a study demonstrated safety and a signal of efficacy at intravesical tacrolimus (LP-10) doses of 4 mg and 8 mg for the treatment for HC, a rare and serious disease. Clinical trial information: NCT01393223 . [Table: see text]
A pan-cancer statistical study of microsatellite instability and Lynch syndrome–associated mismatch repair genes germline mutations.
Authors: Huiya Cao, Suo Peisu, Weishuang Zhang, Guizhen Fang, Yingmei Li, Shifu Chen, Zhang Chunze
Journal: Journal of Clinical Oncology (2023)

10593 Background: Lynch Syndrome (LS), known as hereditary nonpolyposis colorectal cancer (HNPCC1), is caused by germline mutations in the mismatch repair (MMR) genes ( MLH1, MSH2, PMS2, MSH6), or epigenetic silencing of MSH2 which caused by deletion of 3-prime exons of the EPCAM gene and intergenic regions directly upstream of the MSH2 gene. DNA mismatches commonly occur in regions of repetitive nucleotide sequences called microsatellites, and the status of microsatellite instability (MSI) is the key feature in LS-associated cancers. Although there are sporadic reports of MSI and LS in certain cohorts, the real-world status of MSI in large pan-cancer cohort remains to be analyzed. Methods: We retrospectively reviewed all 18189 solid tumor patients from August 1, 2020 to February 5, 2023 from HaploX Genomic Sequencing Center and analyzed their germline mutations in MMR genes ( MLH1,MSH2,PMS2,MSH6 and EPCAM). MSI status was determined using Sanger sequencing or Next-generation sequencing, with tumor MSI status classified as microsatellite instability-high (MSI-H), or microsatellite-stable (MSS). Results: LS-associated germline mutations were detected in 0.313% (n = 57) of patients, and75.4% (n = 43) of patients were identified as MSI-H, and 24.6% (n = 14) of patients were MSS. The patients were grouped into CRC/EC group (colorectal cancer and endometrial cancer) and non-CRC/EC (lung cancer, central nervous system tumor, gastric cancer, esophageal cancer, hepatological cancer, pancreatic adenocarcinoma, small bowel carcinoma, kidney cancer, etc.). Among MSI-H patients, the CRC/EC group accounted for 90.7% (n = 39) and the non-CRC/EC group accounted for 9.3% (n = 4). In MSS patients, the CRC/EC patients accounted for 35.7% (n = 5), and the non-CRC/EC patients accounted for 60% (n = 9). Among patients with MSS, the most frequently mutated gene was MSH6 (n = 9): MSH6 (NM_000179) c.3261dup (p.F1088Lfs*5) mutation was detected in 4 patients, of which 2 patients were paternal and both were diagnosed as colorectal cancer; MSH6 c.718C &gt; T (p.R240*) mutation was detected in 2 patients with available MMR IHC results, and one of them was MSH6 negative in IHC staining. Conclusions: Traditionally, a family history of colorectal cancer or endometrial cancers was the primary clinical feature to diagnose Lynch syndrome. Once it was recognized that Lynch-associated CRCs were microsatellite unstable, tumor testing became an additional tool for identification of Lynch syndrome. Some previous studies also reported Lynch syndrome mutations, primarily MSH6 and PMS2, were present in a few MSS patients. Thus, MSI status or family history as diagnostic factor alone may result in Lynch syndrome under-recognized, and additional NGS test on MMR genes should facilitate more accurate diagnosis.
Effect of insulin resistance on CAC scores in cancer survivors.
Authors: Nicole Jacobi, Syndal Ann Ortman, Lea Buda, Daniel Duprez
Journal: Journal of Clinical Oncology (2023)

e24056 Background: Many cancer (ca) survivors exhibit signs of insulin resistance (IR), an important risk factor for the development of coronary artery disease (CAD). Paramount in survivorship care is prevention of cardiovascular disease. Coronary artery calcium (CAC) scans offer a risk assessment of cardiovascular (CV) disease before cardiac damage has occurred. We investigated how IR affects CAC scores in cancer survivors. We hypothesized that CAC scores differ significantly between insulin-sensitive- and -resistant cancer survivors. Methods: We enrolled 90 cancer survivors of a large community hospital from March 2021 to January 2022 into this pilot study. Patients were subdivided into three groups: insulin-sensitive (IS), insulin-resistant/prediabetic and insulin-resistant/diabetic. Patients were tested for fasting insulin, -glucose, HgbA1c and lipids. Patients without evidence for prediabetes or diabetes also underwent an oral glucose tolerance test (oGTT). All patients received a CAC scan. Results: 32 patients were IS, 29 patients were IR/prediabetic and 29 patients were IR/diabetic. 17 CAC scans in the IS group, 6 CAC scans in the IR/prediabetic group and 5 CAC scans in the IR/diabetic group showed an Agatston score of 0. The p-value between the three groups was statistically significant ( p=0.005) where as the IR/prediabetic- and the IR/diabetic group did not differ statistically from each other. The mean MESA 10-year CHD risk with CAC was 7.8. There was a highly significant difference between the 3 groups: the IS group had a mean of 5.3, the IR/prediabetic group had a mean of 7.3, and the IR/diabetic group had a mean of 11.0 ( p &lt; 0.001). The two IR groups did not differ statistically (p=0.076). Conclusions: Our study showed that IR including prediabetes significantly increases the MESA 10-yr. CHD Risk with CAC in cancer survivors. Survivors with IR also have less frequent zero CAC scores than insulin-sensitive survivors. Survivors disproportionately exhibit insulin resistance, partly due to the association of certain types of cancer with IR. This trial highlights the importance of screening survivors for IR. Survivors diagnosed with IR should be screened for CAD more frequently than the general population. CAC scans are an inexpensive and efficient way of screening asymptomatic cancer survivors for CAD.
Novel biomarkers to predict chronic kidney disease and hypertension at 3 and 12 months post-cisplatin.
Authors: Ryan S T Huang, Kelly McMahon, Stella Wang, Hayton Chui, Asaf Lebel, Jasmine Lee, Vedran Cockovski, Shahrad Rod Rassekh, Kirk R. Schultz, Tom D. Blydt-Hansen, Geoffrey D. E Cuvelier, Cherry Mammen, Maury Pinsk, Bruce C. Carleton, Ross T. Tsuyuki, Colin Ross, Ana Palijan, Michael Zappitelli
Journal: Journal of Clinical Oncology (2023)

e22003 Background: Urine kidney injury biomarkers measured during cisplatin therapy may help identify patients at risk for adverse long-term kidney outcomes. In children treated for cancer, we examined associations of urine tubular injury biomarkers collected during two cisplatin cycles, with chronic kidney disease (CKD) and hypertension at 3 and 12 months post-cisplatin. Methods: We analyzed data from the Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) Nephrotoxicity Study: a twelve-center prospective cohort of 159 children receiving cisplatin. Urine tubular injury biomarkers (by ELISA: neutrophil gelatinase-associated lipocalin [NGAL]; kidney injury molecule-1 [KIM-1]; tissue inhibitor of metalloproteinase-2 [TIMP-2]; insulin-like growth factor-binding protein-7 [IGFBP-7]) were measured at three timepoints (pre-infusion; 12-24 hours post-infusion; discharge after cisplatin cycle) during an early cisplatin cycle (EarlyCisP: first or second cycle of therapy) and a later cycle (LateCisP: last or second-to-last cycle). Area under the curve (AUC) for biomarkers to predict CKD (estimated glomerular filtration rate below normal or urine albumin/creatinine above normal for age, per international definition) and hypertension (3 blood pressures; per American Academy of Pediatrics guidelines) at 3 and 12 months post-cisplatin was calculated. AUC change from adding biomarkers to a published clinical prediction model for 3-month outcomes was evaluated (DeLong method). Results: 156 patients were available for analysis (mainly solid tumors). 3-month (median 90 days) outcomes were 52/118 (44%) CKD; 17/125 (14%) hypertension. 12-month (median 335 days) outcomes were 47/118 (40%) CKD; 15/125 (12%) hypertension. AUCs for all biomarkers to predict 3 and 12-month CKD and hypertension were poor to modest (best AUC = 0.70, 95% CI 0.60-0.80 for pre-infusion EarlyCisP TIMP-2*IGFBP-7 to predict 3-month hypertension). Biomarkers did not improve the clinical prediction model for 3-month CKD (AUC change not statistically significant with vs. without biomarkers). Adding pre-infusion EarlyCisP NGAL and TIMP-2*IGFBP-7 to the clinical prediction model for 3-month hypertension led to AUC change from 0.81 (0.72-0.91) to 0.89 (0.83-0.95) (p &lt; 0.05). Conclusions: Tubular injury biomarkers we studied were individually not strong predictors of 3 or 12-month post-cisplatin kidney outcomes. Adding biomarkers to existing clinical prediction models may help predict post-therapy hypertension development or identify higher kidney-risk patients.